rs9331949

Positions:

• chr8-27597169-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001831.4(CLU):​c.*1072A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0555 in 454,130 control chromosomes in the GnomAD database, including 1,365 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.049 (334 hom., cov: 32)
  • Exomes 𝑓: 0.059 (1031 hom.)
• Consequence: CLU NM_001831.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.278

Genes affected

CLU (HGNC:2095): (clusterin) The protein encoded by this gene is a secreted chaperone that can under some stress conditions also be found in the cell cytosol. It has been suggested to be involved in several basic biological events such as cell death, tumor progression, and neurodegenerative disorders. Alternate splicing results in both coding and non-coding variants.[provided by RefSeq, May 2011]

LOC124901919 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLU	NM_001831.4	c.*1072A>G		3_prime_UTR_variant	9/9	ENST00000316403.15
LOC124901919	XR_007060868.1	n.1500T>C		non_coding_transcript_exon_variant	2/2
CLU	NR_038335.2	n.2677A>G		non_coding_transcript_exon_variant	9/9
CLU	NR_045494.1	n.2602A>G		non_coding_transcript_exon_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLU	ENST00000316403.15	c.*1072A>G		3_prime_UTR_variant	9/9	1	NM_001831.4	P1

Frequencies

GnomAD3 genomes AF: 0.0494 AC: 7522 AN: 152158 Hom.: 334 Cov.: 32

Gnomad AFR AF: 0.0620

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.0158

Gnomad ASJ AF: 0.0280

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.0754

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0268

Gnomad OTH AF: 0.0407

GnomAD3 exomes AF: 0.0617 AC: 8240 AN: 133564 Hom.: 533 AF XY: 0.0687 AC XY: 5011 AN XY: 72890

Gnomad AFR exome AF: 0.0702

Gnomad AMR exome AF: 0.0107

Gnomad ASJ exome AF: 0.0269

Gnomad EAS exome AF: 0.206

Gnomad SAS exome AF: 0.142

Gnomad FIN exome AF: 0.0703

Gnomad NFE exome AF: 0.0279

Gnomad OTH exome AF: 0.0370

GnomAD4 exome AF: 0.0586 AC: 17676 AN: 301854 Hom.: 1031 Cov.: 0 AF XY: 0.0675 AC XY: 11619 AN XY: 172034

Gnomad4 AFR exome AF: 0.0707

Gnomad4 AMR exome AF: 0.0107

Gnomad4 ASJ exome AF: 0.0293

Gnomad4 EAS exome AF: 0.207

Gnomad4 SAS exome AF: 0.141

Gnomad4 FIN exome AF: 0.0668

Gnomad4 NFE exome AF: 0.0290

Gnomad4 OTH exome AF: 0.0463

GnomAD4 genome AF: 0.0494 AC: 7522 AN: 152276 Hom.: 334 Cov.: 32 AF XY: 0.0533 AC XY: 3966 AN XY: 74468

Gnomad4 AFR AF: 0.0620

Gnomad4 AMR AF: 0.0158

Gnomad4 ASJ AF: 0.0280

Gnomad4 EAS AF: 0.214

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.0754

Gnomad4 NFE AF: 0.0268

Gnomad4 OTH AF: 0.0398

Alfa AF: 0.0295 Hom.: 98

Bravo AF: 0.0447

Asia WGS AF: 0.156 AC: 541 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	10
DANN	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9331949; hg19: chr8-27454686;